Bone marrow stem cells which undergo lymphopoiesis are regulated by cell membrane interactions and modulators produced by lymphoid tissues. This study will focus on events associated with early stages of precursor or stem cell differentiation and many of the membrane cell-cell communication events that serve to target factors which potentiate immunogenesis before antigen stimulation. Previously early developing lymphocytes have not been well characterized, and many effects of mixed cell populations raise problems in understanding immunogenesis. Preparatively sorted marrow cells will be analytically and functionally defined. Cell surface-acting and -exchanged molecular complexes will be correlated with differentiation of functionally discrete, biophysically purified classes of developing lymphocytes. Properties for these separations will include intrinsic scatter of laser cytometry based on size, inherent fluorescence, granularity and nuclear density as well as exogenous probes such as fluorochrome stains, labeled liposomes, vesicles and monoclonal antibodies to select determinants. In vitro culture conditions will be further pursued to establish ideal conditions for monitoring and expanding clonal populations while they are studied for interactions and immunomodulators and gamma interferon and other yet-to-be-defined agents which direct acquisition of immunological competence, its expression and control. The objective of this research is to specifically engage control mechanisms responsible for differentiation of stem cell progeny. Selective maturation, induction and interaction of functional lymphoid cells will eventually be used to repair deficiencies, develop stem cell or precursor banks in risk families or individuals with occupational (i.e., irradiation exposure) or life style risks, such as those most likely to be exposed to acquired immune deficiency syndrome (AIDS), and to provide immunological memory capacity for qualitative and quantitative development of the lymphocyte repertoire necessary for responding and regulating immunological activity associated with neoplastic, autoimmune or infectious disease states.